Macular edema is the most common cause of visual loss among patients with uveitis. The goal of this proposal is to address two critical issues in th treatment of uveltic macular edema: 1) the optimal initial treatment for uveitic macular edema; and 2) the optimal treatment of persistent macular edema (i.e. macular edema that has not resolved after initial treatment). Regional corticosteroid injections are the mainstay of treatment for uveitic macular edema. However, there are different routes and formulations, which never have been compared in a trial, and the lack of definitive trials has led to considerable variabilit in clinical practice. For persistent macular edema, repeat injections of corticosteroids typically are administered. However, pilot studies of intravitreal methotrexate and of intravitreal ranibizumab (Lucentis) have suggested efficacy, possibly with fewer ocular side effects than corticosteroid injections, although in the case of ranibizumab possibly with more frequent injections. No comparative trials have been performed of these approaches. The existing MUST Research Group infrastructure will be leveraged to perform two comparative effectiveness clinical trials on the treatment of uveitic macular edema. The specific aims of the trials are: 1) o compare the relative effectiveness of periocular triamcinolone acetonide, intravitreal triamcinolone acetonide (Triescence), and the intravitreal dexamethasone implant (Ozurdex) for the treatment of uveitic macular edema; and 2) to compare the relative effectiveness of intravitreal ranibizumab (Lucentis) and intravitreal methotrexate to the intravitreal dexamethasone implant (Ozurdex) for the treatment of uveitic macular edema that persists after intravitreal triamcinolone injections. The Reading Center has devised and refined grading programs for evaluation of uveitic macular edema throughout the MUST studies and has developed innovative analysis software that will allow integration of data from all study sites despite variation in measurement instruments. Morphologic findings are important for eligibility determination, treatment decisions, and critical endpoints that assist in determining relative efficacy and safety of the various treatment modalities being studied. RELEVANCE: Uveitis is associated with high rates of visual loss, typically caused by structural complications, of which uveitic macular edema is among the most common. Furthermore, macular edema is the most frequent cause of visual loss among patients with uveitis. The two proposed comparative effectiveness trials will provide an evidence base to guide clinicians in the management of uveitic macular edema.